Inhibition of Transient Potassium Current in Cultured and Acutely-
Dissociated Mouse Hippocampal Neurons by GABA A Receptor Activation.
Rui-Lin Wu and Michael E. Barish.
Division of Neurosciences, Beckman Research Institute of the City of Hope,
Duarte, CA 91010.APStracts 3:0025N, 1996.
SUMMARY AND CONCLUSIONS
1. The regulation of A-current, one of several transient voltage-gated
potassium currents, was studied using whole-cell gigaohm seal voltage clamp
techniques on hippocampal pyramidal neurons that were either acutely-
dissociated from postnatal mouse brain or isolated from embryonic mouse brain
and grown in dissociated culture. These neurons also express GABA A receptors,
the activation of which can, under some circumstances, depolarize immature
neurons and the dendrites of more mature neurons. 2. Application of GABA (50
[mu]M) reduced the amplitude of A-current when potassium current amplitude was
measured during a period of slow and incomplete desensitization of I GABA . A-
current was reduced to 67 +/- 9% of control (mean +/- s.d., n = 14) in
acutely-dissociated neurons, and to 64 +/- 11% of control ( n = 15) in
cultured neurons. Similar A-current reductions were seen in large outside-out
membrane patches pulled from somata of cultured neurons, an observation
suggesting that imperfect control of membrane voltage was not responsible for
A-current inhibition. 3. A-current inhibition exhibited the sensitivity
expected of a GABA A -sensitive process. It was mimicked by muscimol, and
blocked by bicuculline, picrotoxin and reduction of [Cl - ] in the external
solution. Baclophen and phaclophen, effective as agonist and antagonist on
GABA B receptors, did not affect A-currents or their inhibition. Reduction in
extracellular osmolarity (to increase cell swelling as might occur with Cl -
entry), or removal of external HCO 3 - (which might flow inward through GABA A
channels and cause local external acidification), did not affect A-current or
its inhibition. The mechanisms of inhibition is not clear at present.
4. We suggest that reduced A-current may favor GABA-induced depolarization and
consequent activation of voltage-gated calcium channels.

Received 4 October 1995; accepted in final form 5 January 1995.
APS Manuscript Number J662-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96